Focal Cerebral Ischemia

Slide 1 · Focal Cerebral Ischemia

Arterial occlusion • cerebral infarction • tissue response

Pathogenesis, vascular mechanisms, gross and microscopic evolution, and clinicopathologic correlations

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Mechanism

Explain how arterial occlusion and collateral flow determine infarct distribution.

Distinguish embolic, thrombotic, and small-vessel causes.

Morphology

Differentiate pale, hemorrhagic, lacunar, and venous infarcts.

Sequence acute, subacute, and remote tissue reactions.

Clinical translation

Relate the anatomic lesion to neurologic deficits.

Recognize the rationale for urgent evaluation of hemorrhage.

Slide 3 · Focal ischemia: The defining event

Partial or complete arterial occlusion

Reduction of local perfusion

Sustained ischemia

Inadequate substrate delivery

Infarction

Death in the supplied territory

Extent depends on duration and collateral flow.

Slide 4 · Focal versus global cerebral ischemia

Focal

One territory or localized region

Often partial/complete arterial occlusion

Deficit tracks anatomic distribution

Global

Widespread perfusion failure or hypoxemia

Generalized vulnerable neural populations

Separate parent-topic entity

The focus of this lecture is focal arterial ischemia.

Slide 5 · Why the brain is highly vulnerable

Strict reliance on aerobic energy production

Disproportionately high oxygen demand for its mass

Ongoing neuronal activity depends on maintained perfusion

Physiologic context

Physiologic parameters: ~1–2% of body mass, ~15% of resting cardiac output, and ~20% of oxygen use.

Slide 6 · Reduced flow is not identical to hypoxemia

Ischemia

Insufficient blood flow into tissue

May result from vessel occlusion or low perfusion pressure

Deprives tissue of circulating substrates

Hypoxemia

Reduced oxygen content of blood

Can occur even without a focal vessel obstruction

Distinguished from local arterial blockade

The focal lesion here arises from impaired arterial delivery.

Slide 7 · Three determinants of infarct extent

Duration

Longer sustained ischemia increases tissue injury.

Magnitude

Severity and speed of flow loss alter survival.

Collateral supply

Alternate pathways may preserve threatened tissue.

Slide 8 · Why equal occlusions need not look alike

Same arterial territory

Comparable primary supply

Different collaterals

Variable residual perfusion

Different final lesions

Size and shape diverge

Ischemic duration adds an independent influence.

Slide 9 · Collateral circulation: Three routes

Circle of Willis

Principal collateral source.

Proximal arterial connections.

External carotid route

Ophthalmic artery collateral contribution.

May supplement intracranial flow.

Leptomeningeal vessels

Variable cortical anastomoses.

Can support distal arterial branches.

Slide 10 · Collateral supply is a network, not a guarantee

Circle of Willis

External carotid–ophthalmic

Leptomeningeal anastomoses

Residual supply to threatened brain

Schematic routes; Contributions vary between individuals.

Slide 11 · Leptomeningeal anastomoses: Distal rescue

Distal ACA, MCA, or PCA branch

Potentially compromised

Surface vessel anastomoses

Inconstant alternative routes

Partially preserved cortical flow

Possible reduction of infarct extent

These interterritorial surface collaterals are anatomically variable.

Slide 12 · Deep penetrating arteries: Limited reserve

Surface cortex

Distal branches may communicate.

Leptomeningeal collaterals can be available.

Variable rescue of distal territory.

Deep structures

Long, deep penetrating vessels.

Little or no effective collateral supply.

Occlusion creates a discrete vulnerable territory.

Deep structures include basal ganglia, thalamus and deep white matter.

Slide 13 · Ischemic tissue exists along a gradient

Irreversibly injured core

Threatened penumbra

Schematic

Conceptual distribution; No fixed dimensions or flow thresholds implied.

Slide 14 · The penumbra is biologically threatened tissue

Located at the transition between necrotic and preserved brain.

Degree and duration of hypoperfusion influence its fate.

Preclinical anti-apoptotic experiments support more than one neuronal death pathway.

Evidence boundary

The cited rescue observations are from animal models—not proof of a specific human treatment.

Slide 15 · Glutamate excitotoxicity in ischemia

Ischemic injury

Abnormal excitatory transmitter release

Excess glutamate

NMDA receptor activation

Ca²⁺ influx

Neuronal cellular damage

Excitotoxicity as an additional CNS-specific ischemic mechanism.

Slide 16 · Neuronal injury: Necrosis and apoptosis

Necrotic injury

Visible eosinophilic neuron death.

Acute structural disruption.

Subsequent tissue removal.

Apoptotic contribution

Suggested by preclinical rescue experiments.

May occur around the injured core.

Not synonymous with gross infarct appearance.

Both mechanisms are considered without assuming exact proportions.

Slide 17 · Three major occlusive etiologies

Embolization

Occlusive material arrives from a remote source.

In situ thrombosis

Thrombus develops at a diseased cerebral artery.

Vascular inflammation

Vessel injury leads to narrowing and thrombosis.

Slide 18 · Embolization: A remote source, a local infarct

Source vessel or heart

Thrombotic or nonthrombotic material

Arterial transport

Movement with blood flow

Intracranial lodging

Abrupt branch obstruction

An embolic event usually localizes where vessel caliber or geometry traps material.

Slide 19 · Cardiac mural thrombi as embolic sources

Cardiac mural thrombus is a major source of cerebral emboli.

Associated settings include myocardial infarction and atrial fibrillation.

Valvular disease also predisposes to embolization.

Causal link

An embolus from the heart can obstruct an otherwise distant cerebral artery.

Slide 20 · Cardiac conditions alter cerebral embolic risk

Myocardial infarction

Predisposes to mural thrombus.

A potential source for distant embolization.

Atrial fibrillation

An important embolic predisposition.

The source can remain outside the brain.

Valvular disease

A recognized cardiac source category.

Requires distinguishing from local cerebral thrombosis.

Slide 21 · Artery-to-artery embolization

Carotid atheromatous plaque

Potential thromboembolic source

Detached material

Enters intracranial flow

Distal branch occlusion

Embolic cerebral infarct

Carotid plaques are an important noncardiac source.

Slide 22 · Paradoxical and procedure-related emboli

Paradoxical emboli

Systemic venous thrombus accesses arterial circulation.

Children with congenital heart disease.

Cardiac procedures

Cardiac surgery may be followed by thromboembolism.

Mechanism remains embolic, not necessarily in situ cerebral thrombosis.

Both are less typical than cardiac mural or carotid sources in the source text.

Slide 23 · Nonthrombotic emboli

Fat or marrow

Trauma/fracture-associated shower of emboli.

Air

An embolic material explicitly listed.

Tumor

Another nonthrombotic source of arterial obstruction.

Slide 24 · Why the middle cerebral artery is often affected

The MCA is a direct continuation of internal carotid flow.

Its vascular territory is the most frequent site of embolic infarction in the source.

Embolic infarction affects both hemispheres with approximately equal frequency.

Distribution matters

Site of vascular obstruction predicts the lesion more closely than the distant embolic source.

Slide 25 · Emboli preferentially lodge at branch points

Flowing embolus

Lodging at branching point

Arterial branching and pre-existing narrowing are favored sites of lodging.

Slide 26 · Shower embolization is a different pattern

Single major embolus

A dominant occluded artery.

A localized arterial territory.

Focal neurologic dysfunction is often evident.

Multiple small emboli

Many distal vascular occlusions.

More widespread dysfunction.

May lack clear localizing signs.

The second pattern is described in fat embolism after fractures.

Slide 27 · Marrow/fat embolization after trauma

Bone fracture or trauma

Marrow contents may enter circulation

Shower of emboli

Numerous small cerebrovascular events

Widespread white-matter lesions

Often hemorrhagic; Diffuse cortical dysfunction

Higher cortical dysfunction and impaired consciousness can occur without focal signs.

Slide 28 · In situ arterial thrombosis

Atheromatous plaque

Vulnerable arterial lesion

Acute plaque change

Local thrombus formation

Luminal obstruction

Distal cerebral ischemia

The source identifies altered atherosclerotic plaque as the common mechanism.

Slide 29 · Vulnerable plaque: Local mechanism

Plaque

Local thrombus

Arterial lumen

Schematic arterial lumen: Not a pathologic specimen.

Slide 30 · Common sites of cerebral atherothrombosis

Carotid bifurcation

Atherosclerosis-prone branching site.

May obstruct flow or generate emboli.

MCA origin

Proximal major intracranial artery.

Direct downstream arterial territory.

Basilar artery ends

Both ends are named vulnerable sites.

Occlusion affects posterior circulation.

Slide 31 · Thrombus can evolve in three ways

Progressive narrowing

Increasing local restriction of blood flow.

Anterograde extension

Thrombus propagates along the vessel.

Distal embolization

Fragmentation seeds downstream branches.

Slide 32 · Atherosclerotic disease: Systemic associations

Hypertension and diabetes commonly coexist with cerebrovascular atherosclerosis.

Cerebral occlusive disease therefore often reflects systemic vascular pathology.

Risk association does not specify whether a given infarct is thrombotic or embolic.

Diagnostic interpretation

The vascular lesion and distribution remain essential to mechanism attribution.

Slide 33 · Hypertensive small-vessel disease

Chronic hypertension

Deep arterial injury

Arteriolosclerosis

Small-vessel luminal disease

Thrombotic occlusion

Small deep cerebral infarct

Arterioles and small arteries supplying deep CNS structures are involved.

Slide 34 · Small-vessel caliber in the source

Implicated arteries as approximately 40–900 μm in diameter.

Affected vessels supply basal ganglia, hemispheric white matter, and brainstem.

This is a morphologic small-vessel disease category, distinct from major carotid occlusion.

Scope

The caliber range is explicitly from the textbook; Not a proposed diagnostic cutoff for imaging.

Slide 35 · Deep small-vessel territories

Deep gray nuclei

Putamen and globus pallidus.

Thalamus and caudate nucleus.

White matter

Internal capsule.

Other hemispheric deep white matter.

Brainstem

Pons is a characteristic location.

Deficits depend on the tract or nucleus involved.

Slide 36 · How a lacune forms

Penetrating-artery disease

Arteriolosclerosis ± thrombosis

Complete occlusion

Small deep area of ischemia

Tissue removal

Cavity with surrounding gliosis

A small lacunar infarct can be clinically silent or severely disabling.

Slide 37 · Lacunar infarct: Anatomic distribution

The source lists putamen, globus pallidus, thalamus, internal capsule, deep white matter, caudate, and pons.

Several lesions may coexist in deep brain regions.

Clinical impact is governed by exact location, not merely small size.

Interpretation

A lesion involving critical deep tracts can cause substantial impairment.

Slide 38 · Gross and microscopic lacunar morphology

Gross appearance

Small lake-like cavitary lesion.

A conventional largest dimension below 15 mm.

Can be single or multiple.

Microscopic appearance

Definite loss of brain parenchyma.

Gliosis around the tissue defect.

Consistent with a healed small infarct.

The <15 mm definition is the supplied textbook convention.

Slide 39 · État criblé is not a lacunar infarct

État criblé

Widened perivascular spaces.

No tissue infarction is required.

Associated with diseased deep small vessels.

Lacunar infarct

Ischemic tissue destruction has occurred.

A true cavitary defect remains.

Surrounding reactive gliosis is present.

A dilated space should not automatically be labeled an infarct.

Slide 40 · Small-vessel cavities: Interpret the tissue

Parenchymal cavity / space

Surrounding gliosis

Schematic

A lacune represents tissue loss; A widened perivascular space does not by itself establish infarction.

Slide 41 · Vasculitis can obstruct cerebral flow

Vessel-wall inflammation

Injury to small or large vessels

Luminal narrowing ± thrombosis

Reduced downstream arterial flow

Cerebral infarction

Single or multiple lesions

Both infectious and noninfectious vascular inflammation are recognized.

Slide 42 · Infectious vasculitic causes

Syphilis

Named classic infectious cause.

May involve cerebral vessels.

Tuberculosis

Another named infectious cause.

Potential vessel inflammation and occlusion.

Opportunistic fungi

Aspergillosis is a listed example.

Relevant particularly with immunosuppression.

Slide 43 · Noninfectious cerebral vasculitis

Systemic inflammatory disease

Polyarteritis nodosa is a cited example.

Other vasculitides may involve brain vessels.

Infarcts may be multiple.

Primary angiitis of the CNS

Vasculitis develops in the CNS.

It may exist without systemic vasculitis.

Produces cerebral ischemia through vessel injury.

No modern diagnostic criteria are imported beyond the supplied text.

Slide 44 · Additional thrombotic/occlusive conditions

Hypercoagulability

Can promote thrombosis.

May also contribute to venous events.

Cervical arterial dissection

Extracranial neck vessels can dissect.

Downstream cerebral perfusion may suffer.

Substance exposure

Amphetamines, heroin and cocaine are listed.

Associated with vascular occlusive events.

Slide 45 · Cerebral infarcts: Two morphologic patterns

Nonhemorrhagic

Often begins pale or anemic.

Typical initial occlusive pattern.

Tissue softening and necrosis develop.

Hemorrhagic

Secondary extravasation of blood.

Often reflects reperfusion of damaged vessels.

May be punctate or confluent.

Both are ischemic infarcts; The labels describe secondary hemorrhage.

Slide 46 · Why occlusive infarcts usually begin pale

Arterial end-organ supply

Limited alternative inflow

Persistent arterial occlusion

Low perfusion of involved tissue

Nonhemorrhagic infarct

Initial pale/anemic pattern

A nonhemorrhagic lesion can later undergo hemorrhagic transformation.

Slide 47 · Hemorrhagic transformation: Causal sequence

Prolonged ischemia

Small-vessel structural injury

Recanalization/reperfusion

Spontaneous or therapeutic restoration

Blood extravasation

Punctate or confluent hemorrhages

Reperfusion injury explains secondary hemorrhage within an infarct.

Slide 48 · Recognizing the reperfused lesion

Ischemic tissue

Punctate blood

Schematic only. Red marks denote potential punctate secondary hemorrhage—not actual gross pathology.

Slide 49 · Anticoagulation and hemorrhagic extension

Hemorrhagic infarcts include extravasated blood with subsequent resorption.

Extensive intracerebral hematomas may occur in anticoagulated individuals.

A hemorrhagic component materially changes acute treatment considerations.

Clinical safety

Robbins specifically cautions against thrombolysis when brain hemorrhage is present.

Slide 50 · Cerebral venous infarcts

Venous sinus or deep-vein thrombosis

Outflow obstruction

Venous congestion

Disrupted microvascular drainage

Venous infarct

Often hemorrhagic

Superior sagittal sinus, other sinuses and deep cerebral veins are cited.

Slide 51 · Venous infarction: Predisposing settings

Hypercoagulability

Systemic propensity to thrombosis.

A listed contributor to venous occlusion.

Neoplasm

Cancer-associated clotting tendency can raise risk.

Context affects diagnostic suspicion.

Local infection

Another potential prothrombotic setting.

Outflow obstruction can lead to hemorrhagic infarction.

Slide 52 · Arterial and venous mechanisms compared

Arterial occlusion

Failure of inflow.

Typically initially pale.

May hemorrhage after reperfusion.

Venous thrombosis

Failure of outflow.

Venous infarction is often hemorrhagic.

Sinus/deep vein obstruction is characteristic.

Gross hemorrhage alone does not identify the original vascular cause.

Slide 53 · Gross appearance changes over time

0–6 h

Little gross change

~48 h

Pale, soft, swollen

2–10 d

Gelatinous, friable

10 d–3 wk

Liquefaction → cavity

Slide 54 · First six hours: Subtle gross appearance

Even with irreversible injury, little gross change may be visible.

A visually normal-looking region does not rule out early ischemic injury.

Histologic changes and gross changes follow different time courses.

Observation

The first hours are a poor interval for gross recognition of infarction.

Slide 55 · Around 48 hours: Edema and pallor

Infarcted tissue

Pallor

Increased tissue water

Swelling and softness

Architecture blurred

Loss of visible gray–white boundary

The infarct becoming pale, soft and swollen by roughly 48 hours.

Slide 56 · Days 2–10: Friability develops

Dead tissue becomes gelatinous and friable.

Infarct boundary becomes easier to appreciate.

Resolution of adjacent viable-tissue edema sharpens the interface.

Why the border appears

The evolving distinction is partly due to reduction of edema outside the lesion.

Slide 57 · Days 10–21: Liquefaction and cavitation

Progressive tissue digestion

Brain parenchyma softens

Removal of necrotic material

Fluid-filled defect develops

Cavity expansion

Continues as dead tissue is cleared

The cavity is the end result of tissue loss, not a restored normal cortex.

Slide 58 · Gross evolution integrates two processes

Early injury

Loss of perfusion and cell damage.

Pallor, swelling, and softening.

Tissue remains present but nonviable.

Later cleanup

Phagocytosis and liquefaction.

Removal of damaged parenchyma.

Development of a residual cavity.

Timing is approximate and varies within and between lesions.

Slide 59 · Acute microscopy: Red neurons

~6–12 h after injury

Neuronal eosinophilia becomes evident

Nuclear injury

Pyknosis and karyorrhexis

Neuronal necrosis

“Dead red neurons”

Schematic chronology; No photomicrograph has been reproduced.

Slide 60 · “Dead red neuron”: Components of the sign

Cytoplasm

Greater eosinophilia.

Associated neuronal shrinkage.

Nucleus

Pyknosis and karyorrhexis.

Irreversible nuclear injury.

Context

Acute ischemic neuronal necrosis.

Needs clinical-anatomic correlation.

Slide 61 · Acute edema involves cells and interstitium

Cytotoxic edema

Cellular swelling during ischemic injury.

Neurons and glia are vulnerable.

Coexists with other early changes.

Vasogenic edema

Fluid accumulation outside cells.

Occurs concurrently in acute infarcts.

Contributes to gross swelling.

Both forms are described in the acute infarct phase.

Slide 62 · Early glial and myelin injury

Astrocytes and endothelial cells swell in the acute lesion.

Normal staining distinction between gray and white matter is lost.

Myelinated fibers begin to disintegrate.

Tissue-level message

Neuronal death is not the only component of infarct evolution.

Slide 63 · Neutrophils enter during early infarction

First day

Neuronal necrosis

Up to ~48 h

Increasing neutrophils

Thereafter

Neutrophils decline

Slide 64 · Macrophages and microglia arrive

~48–72 h

Circulating monocytes and microglia

Phagocyte accumulation

Removal of dead elements

Next 2–3 weeks

Phagocytes become predominant

Macrophage-dominant cleanup distinguishes evolving from very early lesions.

Slide 65 · Foamy macrophages signal cleanup

Macrophages ingest degraded myelin and sometimes blood products.

Their cytoplasm becomes laden with phagocytosed material.

They may remain within the lesion for months or years.

Interpretive value

A lipid-laden macrophage population supports an organizing infarct in context.

Slide 66 · Peripheral astrocytosis and neovascularization

~1 week at the lesion edge

Reactive astrocytes and new vessels appear

During liquefaction

Astrocytes enlarge and proliferate

Reparative rim

Glial processes form a denser network

Reparative reactions are especially prominent at the infarct margin.

Slide 67 · Remote infarct: Cyst cavity and glial rim

Parenchymal cavity / space

Surrounding gliosis

Schematic

Schematic healed infarct: Parenchymal loss surrounded by gliosis and capillaries.

Slide 68 · The cortex retains a gliotic boundary

In a remote cortical infarct, the cavity is separated from meninges by gliotic tissue.

The residual layer derives from the cortical molecular layer.

Pia and arachnoid are not directly destroyed by the infarct in this description.

Morphologic point

A fluid-filled parenchymal cavity need not be continuous with subarachnoid space.

Slide 69 · Evolution occurs from the edge inward

Central debris clearance

Peripheral gliosis and repair

Schematic

Schematic process: A single infarct can show different apparent ages in adjacent zones.

Slide 70 · Histologic stages: A diagnostic comparison

Stage

Approximate period

Dominant findings

Acute

~6–48 hours

Red neurons, edema, neutrophils

Evolving

~48 hours to weeks

Microglia/macrophages, then astrogliosis

Remote

After months

Cyst cavity with gliotic, vascularized rim

Slide 71 · The clock is approximate, not absolute

Reactions overlap and are spatially heterogeneous.

The periphery may organize while the center remains in an earlier cleanup phase.

Use morphology and anatomic context rather than assigning a single exact hour.

Practical principle

Progression from infarct edge to center.

Slide 72 · Clinical deficit reflects the damaged territory

Arterial obstruction

A specific perfusion territory

Parenchymal injury

Loss of functions represented there

Neurologic deficit

Distribution-dependent manifestations

Cause alone does not predict signs; Localization matters.

Slide 73 · Symptoms usually develop rapidly

Neurologic manifestations often start over minutes.

The deficit may continue to evolve over hours.

Time course plus focal neurologic distribution prompts urgent vascular assessment.

Clinical correlation

The presentation reflects rapidly evolving tissue damage and its territory.

Slide 74 · Clinical severity need not track lesion diameter

Small strategic infarct

May interrupt essential deep pathways.

Lacunes can cause severe neurologic dysfunction.

Small nonstrategic infarct

May remain clinically silent.

Anatomic location remains decisive.

Robbins explicitly contrasts silent and disabling lacunar infarcts.

Slide 75 · Recovery has more than one substrate

At-risk tissue

Some threatened tissue may recover.

Penumbra preservation is biologically important.

Surrounding edema

Edema resolution may improve function.

Changes can occur without replacing dead neurons.

Longer evolution

Slow recovery can continue for months.

Extent depends on initial injury.

Slide 76 · Why hemorrhage assessment is urgent

No hemorrhage demonstrated

A nonhemorrhagic arterial infarct is possible.

Urgent reperfusion decisions can be relevant.

Brain hemorrhage present

Management materially differs.

Thrombolysis is contraindicated with intracranial hemorrhage.

This is pathology-level rationale—not a treatment protocol or eligibility checklist.

Slide 77 · Applied case: Sudden focal dysfunction

Clinical vignette

A patient develops an abrupt focal neurologic deficit. A cardiac mural thrombus is identified.

Which pathogenesis best explains a new MCA-territory infarct?

Cardioembolism: A heart-derived thrombus travels distally and obstructs a cerebral artery.

Mural thrombus provides a distant source.

MCA territory is a common embolic destination.

Anatomic localization predicts the deficit.

Slide 78 · Applied case: Small deep cavity

Clinical vignette

A patient with longstanding hypertension has a small healed cavitary lesion in the internal capsule.

What vascular process and microscopic rim are expected?

Deep penetrating-artery small-vessel disease causing a lacunar infarct, with surrounding gliosis.

Hypertension affects penetrating vessels.

Lacunes are small tissue-loss cavities.

A strategic deep location can be clinically important.

Slide 79 · Applied case: Secondary hemorrhage

Clinical vignette

An initially pale arterial infarct later contains punctate hemorrhages after vessel recanalization.

Which mechanism links the two appearances?

Hemorrhagic transformation from reperfusion of previously injured microvessels.

Prolonged ischemia injures small vessel walls.

Restored flow permits extravasation.

This is not synonymous with primary vessel rupture.

Slide 80 · Integrated pathogenesis and tissue response

Vascular event

Embolic, thrombotic, inflammatory, or small-vessel

Local ischemia

Magnitude, duration, collaterals

Tissue injury

Neuronal death ± reperfusion hemorrhage

Healing

Phagocytosis → gliotic-rimmed cavity

Lesion anatomy determines the neurologic syndrome.

Slide 81 · Key distinctions to retain

Mechanism

Embolus travels; Thrombus forms locally.

Surface collaterals differ from deep vessels.

Morphology

Pale and hemorrhagic describe blood content.

Lacune requires parenchymal tissue loss.

Timeline

Red neurons early; Macrophages later.

Remote lesions cavitate with gliosis.

Slide 82 · Primary reference and source boundaries

Robbins, Cotran & Kumar: Pathologic Basis of Disease, 11th ed. (2026)

Chapter 28 · The Central Nervous System

Focal cerebral ischemia; adjacent hypoxia/ischemia and cerebrovascular disease context

No chapter PDF or licensed textbook micrographs were supplied. Illustrations here are original editable schematics, not diagnostic images.